The 2.2-kb promoter of cartilage-derived retinoic acid-sensitive protein controls gene expression in cartilage and embryonic mammary buds of transgenic mice.

ABSTRACT

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein primarily expressed in chondrocytes. Pathologically, CD-RAP is detected in melanoma, chondrosarcoma and breast cancer. As an approach to define the transcriptional regulatory domains responsible for induction of chondrocyte activity in vivo, we generated transgenic mice harboring various fragments of the mouse CD-RAP promoter linked to the Escherichia coli beta-galactosidase gene. Analysis of the transgene expression pattern by X-gal staining indicates that 2251 bp of the CD-RAP 5'-flanking sequence generates beta-galactosidase activity in all cartilage in embryos and adult animals. In addition, we also detected transient X-gal staining in mammary gland primordium from day 11.5 to 15.5 of gestation. Histological examination revealed that the transgene is located in the chondrocytes of cartilage and the epithelial cells of mammary buds. The cartilage transgene expression pattern is consistent with that of endogenous CD-RAP gene expression. The presence of beta-galactosidase in the mammary buds led us to the demonstration of a unique pattern of transient endogenous expression of CD-RAP in the mammary bud. The finding of transient CD-RAP expression in mammary buds suggests that it may play a role in the organogenesis of mammary glands.